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Valspodar is a potent inhibitor of P-glycoprotein (P-gp) widely used in preclinical and clinical studies [1].

P-gp is a transmembrane glycoprotein which is located on cell membrane. P-gp distributes extensively and is expressed in certain cell types primarily containing liver, colon, kidney and pancreas. It also is known as multidrug resistance protein 1 (MDR1) which is pumps foreign substances out of cells. P-gp decreases the net uptake of cytotoxic drugs into the cells and mediats the efflux of these agents out of the cells, which is ATP-dependent. P-gp also overexpress in some cancer cells. P-gp plays an important role in mediating resistance to anticancer drugs and decreasing drug accumulation in multidrug-resistant cancer cells.[1]

Valspodar can reverse the resistance to mitoxantrane which is due to the expression of P-gp. The IC50 of mitoxantrane decreased from 1.6 ± 0.13 μM to 0.4 ± 0.02

μM in MDA-MB-435mdr cells pretreated with 3 mg/ml PSC. Valspodar increase the mitoxantrane intracellular accumulation by decreasing drug efflux and increasing mitoxantrone net uptake in cells.[1] The cytotoxicity was significant greater in T47D/TAMR-6 cells treated with doxorubicin and valspodar than doxorubicin only. Co-encapsulation of doxorubicin and valspodar presents a promising anticancer effect.[2] Valspodar was rapid absorpted and reachs  the  peak  within  2 hnafter an oral dose. Valspodar showed properties of wide distribution, low hepatic extraction and mean bioavailability of 42.8% in rat.[3]

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